Methods and pharmaceutical compositions for treating microbiome dysregulations associated with circadian clock disruption

Abstract

The present invention relates to the treatment of microbiome dysregulations. Said dysregulations may subsequently contribute to the development of several chronic diseases. Thus characterization of new post-biotic compounds inducing beneficial changes on host-microbiota interactions may be highly desirable. The inventors showed that Nlrp6 diurnally coordinates cyclical adaptation of the gut microbiota diversity to epithelial plasticity in response to a treatment with a Csnk2 inhibitor. The invention therefore relates to an inhibitor of Csnk2, for use in the treatment of microbiome dysregulations notably associated with circadian clock disruption. Said inhibitor may be selected among chemically synthesized or natural selective Csnk2 inhibitors such as flavones.

The invention claimed is: 
     
       1. A method for treating dysbiosis associated with circadian clock disruption in a subject in need thereof, said method comprising steps of
 selecting a subject having dysbiosis associated with circadian clock disruption wherein said dysbiosis is characterized by a change and/or loss of diurnal variation of the gut microbiota, wherein said subject has an increased level of harmful gut bacteria and a reduced level of beneficial gut bacteria, and wherein the beneficial gut bacteria are selected from at least one of non-flagellated and butyrate-producing bacteria belonging to bacteroidetes phylum and the harmful gut bacteria are  Ruminococcus gnavus  or  Proteus mirabilis  bacteria; and 
 administering to the subject an inhibitor of the casein kinase 2 (Csnk2) activity. 
 
     
     
       2. The method according to  claim 1 , wherein microbiome dysregulation includes dysbiosis and/or loss of diurnal rhythmicity of the gut microbiota. 
     
     
       3. The method according to  claim 1 , wherein the subject suffers from or is at risk of a circadian rhythm sleep disorder. 
     
     
       4. The method according to  claim 1 , wherein the inhibitor of the casein kinase 2 (Csnk2) activity is selected among flavones, tyrphostins and their derivatives. 
     
     
       5. The method according to  claim 1 , wherein the inhibitor of the casein kinase 2 (Csnk2) activity is selected from the group consisting in apigenin, luteolin, and tyrphostin AG99. 
     
     
       6. The method according to  claim 1 , wherein said non-flagellated and butyrate-producing bacteria belonging to bacteroidetes phylum are selected from  Alistipes, Banesiella  and  Allobaculum  bacteria.